Rebamipide Nanosuspension Loaded In Situ Gel: A Promising Strategy to Improve Ocular Delivery and Treatment of Dry Eye Disease.

PURPOSE: Rebamipide (REBA) is used in the treatment of dry eye disease (DED) and is available as Mucosta® ophthalmic suspension that is widely used in Japan. However, certain challenges such as blurred vision, less permeation due to large particle size, frequent administration because of nasolacrimal drainage, and bitter taste were observed after topical instillation. So, in this study, rebamipide nanosuspension (REBA-NS) bearing in-situ gel (REBA-NS gel) was developed for addressing the challenges as well as ease of application. METHODS: REBA-NS was prepared using the acid-base neutralization method, employing HPMC as a stabilizer and optimized using the quality-by-design approach. Further characterization and evaluation of REBA-NS was carried out, and the optimized REBA-NS was loaded to gel using gellan gum, which has a property of forming an in-situ gel after contact with the simulated tear fluid. Finally, the in-vitro and in-vivo studies of the REBA-NS gel were performed. RESULTS: REBA-NS exhibited nanosized particles (<270 nm) that may help in enhanced permeation, low polydispersity index (<0.25) with high drug content (>80%). Moreover, the REBA-NS gel exhibited mucoadhesiveness, sustained drug release, sterile nature, optimum pH (∼7.2), and osmolality (∼216 mOsm/kg) required for ocular administration, which may aid in the retention of REBA. Finally, REBA-NS gel on the DED-induced rats depicted an increased tear secretion and decreased corneal fluorescein scoring by 1.39-folds and 9.12-folds, respectively, compared to the REBA solution on day 7 of treatment. CONCLUSION: In a nutshell, REBA-NS gel was found to be a promising approach for treating DED.